Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.

P A Würtzen; Mogens Holst Nissen; M H Claesson

Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.

P A Würtzen, Mogens Holst Nissen, M H Claesson

Department of Immunology and Microbiology

30 Citations (Scopus)

Abstract

Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.

Original language	English
Journal	Scandinavian Journal of Immunology
Volume	53
Issue number	6
Pages (from-to)	579-87
Number of pages	8
ISSN	0300-9475
Publication status	Published - 2001

Cite this

Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production. / Würtzen, P A; Nissen, Mogens Holst ; Claesson, M H.

In: Scandinavian Journal of Immunology, Vol. 53, No. 6, 2001, p. 579-87.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{3e383350ba3011ddae57000ea68e967b,

title = "Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.",

abstract = "Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.",

author = "W{\"u}rtzen, {P A} and Nissen, {Mogens Holst} and Claesson, {M H}",

note = "Keywords: Antigen Presentation; Antigens, Differentiation, Myelomonocytic; CD40 Ligand; Cell Differentiation; Cells, Cultured; Cytokines; Dendritic Cells; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Monocytes; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Tuberculin; Tumor Necrosis Factor-alpha",

year = "2001",

language = "English",

volume = "53",

pages = "579--87",

journal = "Scandinavian Journal of Immunology, Supplement",

issn = "0301-6323",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.

AU - Würtzen, P A

AU - Nissen, Mogens Holst

AU - Claesson, M H

N1 - Keywords: Antigen Presentation; Antigens, Differentiation, Myelomonocytic; CD40 Ligand; Cell Differentiation; Cells, Cultured; Cytokines; Dendritic Cells; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Monocytes; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Tuberculin; Tumor Necrosis Factor-alpha

PY - 2001

Y1 - 2001

N2 - Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.

AB - Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.

M3 - Journal article

C2 - 11422906

SN - 0301-6323

VL - 53

SP - 579

EP - 587

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

IS - 6

ER -

Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.

Abstract

Fingerprint

Cite this